miR-137 Inhibits the Invasion of Melanoma Cells through Downregulation of Multiple Oncogenic Target Genes
miR-137 Inhibits the Invasion of Melanoma Cells through Downregulation of Multiple Oncogenic Target Genes
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DOI：
10.1038/jid.2012.357
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发表时间：
2013-03-01
影响因子：
6.5
通讯作者：
Eichmueller, Stefan B.
中科院分区：
文献类型：
--
作者：
Luo, Chonglin;Tetteh, Paul W.;Eichmueller, Stefan B.
MicroRNAs是一种小的非编码RNA，调节基因表达，在各种类型的癌症中发挥重要作用。此前，miR-137被报道在包括恶性黑色素瘤在内的不同癌症中发挥肿瘤抑制作用。在这项研究中，我们表明miR-137的低表达与IV期黑色素瘤患者的低生存率相关。我们确认了两个基因(c-Met和YB1)是miR-137的直接靶点，并确认了两个已知的靶点，即Zust增强子同源基因2(EZH2)和小眼球相关转录因子(MITF)。功能研究表明，miR-137通过下调多个靶基因来抑制黑色素瘤细胞的侵袭。MiR-137过表达可通过小干扰RNA敲除EZH2、c-Met或Y盒结合蛋白1(YB1)而降低侵袭力。此外，miR-137还能抑制黑色素瘤细胞的迁移和增殖。最后，miR-137诱导黑色素瘤细胞系凋亡，并降低bcl2水平。综上所述，我们的研究证实了miR-137在恶性黑色素瘤中发挥了肿瘤抑制作用，并揭示了nniR-137调节多个靶点，包括c-Met、YB1、EZH2和MITF。《皮肤病研究杂志》(2013年)133768-775；doi：10.1038/jid.2012.357；2012年11月15日在线发布
MicroRNAs are small noncoding RNAs that regulate gene expression and have important roles in various types of cancer. Previously, miR-137 was reported to act as a tumor suppressor in different cancers, including malignant melanoma. In this study, we show that low miR-137 expression is correlated with poor survival in stage IV melanoma patients. We identified and validated two genes (c-Met and YB1) as direct targets of miR-137 and confirmed two previously known targets, namely enhancer of zeste homolog 2 (EZH2) and microphthalmia-associated transcription factor (MITF). Functional studies showed that miR-137 suppressed melanoma cell invasion through the downregulation of multiple target genes. The decreased invasion caused by miR-137 overexpression could be phenocopied by small interfering RNA knockdown of EZH2, c-Met, or Y box-binding protein 1 (YB1). Furthermore, miR-137 inhibited melanoma cell migration and proliferation. Finally, miR-137 induced apoptosis in melanoma cell lines and decreased BCL2 levels. In summary, our study confirms that miR-137 acts as a tumor suppressor in malignant melanoma and reveals that nniR-137 regulates multiple targets including c-Met, YB1, EZH2, and MITF. Journal of Investigative Dermatology (2013) 133, 768-775; doi:10.1038/jid.2012.357; published online 15 November 2012